Synthesis of 4-trifluoromethanesulfonate substituted 3,6-dihydropyrans and their application in various C-C coupling reactions

Article abstract of DOI:10.1039/c6ra02343f

The triflic acid mediated Prins cyclization of homopropargylic alcohols with aldehydes afforded 3,6-dihydro-2H-pyran-4-yl trifluoromethanesulfonates efficiently and highly regioselectively. The dihydropyran thus formed is transformed into different 4-alkyl and aryl substituted products using Suzuki, Heck, Stille and Sonogashira coupling reactions.

Full text of DOI:10.1039/c6ra02343f

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ARTICLE TYPE
Synthesis of 4-trifluoromethanesulfonate substituted 3,6-dihydropyrans
and their application in various C-C coupling reactions
Anil K. Saikia,*a Priya Ghosha and Ashutosh K. Kautarya a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
economical method is of value to organic chemists. There are
different methods towards the construction of dihydropyrans
50 including heteroꢀDielsꢀAlder reactions,15 olefin metathesis,16
base promoted cyclizations of sulfenyl dienols,17 oxoniumꢀene
reactions,18 [4+2] annulations,19 intramolecular CꢀC bond
formation of alkyneꢀepoxide,20 and Prins cyclization reactions.21
Among various methods available, Prins cyclization is considered
55 to be the most convenient tool as it provides the desired product
in a single step with high diastereoselectivity. On the other hand,
one pot, multi component and selective reactions are considered
as green synthetic routes.22 Considering these and in continuation
of our research on Prins cyclization reaction,23 herein, we report a
60 one pot, three component and highly selective Prins cyclization
reaction for efficient synthesis of 3,6ꢀdihydroꢀ2Hꢀpyranꢀ4ꢀyl
trifluoromethaneꢀsulfonates from homopropargylic alcohols and
aldehydes mediated by triflic acid in which triflic acid acts as
Brønsted acid as well as a nucleophile. Although there are several
65 reports which illustrate the preparation of 4ꢀhalotetrahydropyran
derivatives, there are only a couple of reports which demonstrated
the preparation of 4ꢀhaloꢀ3,6ꢀdihydroꢀ2Hꢀpyrans mediated by
Lewis acids. Use of Fe(III) salts by Martin and coꢀworkers have
resulted in 2ꢀalkylꢀ4ꢀhaloꢀ3,6ꢀdihydroꢀ2Hꢀpyrans.9g,21h,i The
70 presence of the triflate group at the vinylic position of
dihydropyran ring, which can be used in many coupling
reactions, has not been reported so far.
Triflic acid mediated Prins cyclization of homopropargylic
alcohols with aldehydes afforded 3,6-dihydro-2H-pyran-4-yl
trifluoromethanesulfonates
efficiently
and
highly
regioselectively. The dihydropyran thus formed is
10 transformed into different 4-alkyl and aryl substituted
products using Suzuki, Heck, Stille and Sonogashira coupling
reactions.
Introduction
Substituted pyran motifs constitute the core structural unit in
15 numerous biologically active natural products such as calixyn L,1
ambruticin,2 kendomycin3 (Figure 1) and have diverse
applications in cosmetics and agro chemicals as well.4 The
dihydropyran skeleton of this family is distinctly important since
functionalized dihydropyrans are versatile building blocks widely
20 used in the synthesis of biologically active molecules5 and this
structural moiety exists in many natural products such as
laulimalide6 and aspergillide C (Figure 1).7 The presence of
double bond in cyclic system is not only responsible for their
biological properties but also serve as a functional group for
25 further manipulations in organic synthesis.8 They can also be
used as building blocks in organic synthesis.9 Triflates, present at
vinylic position, in general are valuable substrates for a number
of organic reactions such as electrophilic aromatic substitution
reaction10 and various metal catalyzed crossꢀcoupling reactions
30 such as Suzuki,11 Heck,12 Stille,13 and Sonogashira coupling.14
Therefore, the synthesis of such valuable units in an easier and
Results and discussion
75
To start with homopropargyl alcohol
benzaldehyde 2a (1.0 equiv) were treated with 1.2 equivalents of
triflic acid in dry dichloromethane at room temperature for 12 h
1 (1.5 equiv) and
HO
OH
Me
Me Me
H
O
H
H
O
O
Et
HO2C
H
and
3,6ꢀdihydroꢀ2ꢀphenylꢀ2Hꢀpyranꢀ4ꢀyl
trifluoromethaneꢀ
35
40
45
OH
Me
HO
HO
OH
OH
80 sulfonate 3a was obtained in 92% yield. The reaction is
regioselective and only 3,6ꢀdihydropyrans was formed in the
reaction. The stereochemistry of the compounds was determined
ambruticin
O
OMe
calixyn L
1
by H, 13C, DEPT and HMQC analysis. Finally the structure is
Me
Me
Me
confirmed by Xꢀray crystallographic analysis (Figure 2).24 The
85 scope of the reaction was examined with variety of aliphatic and
aromatic aldehydes (Table 1). It was observed from the Table 1
that both aromatic and aliphatic aldehydes gave the good yields.
Aromatic aldehydes are better substrates than the aliphatic
substrates. There is no major role of electron withdrawing and
90 donating groups on the aromatic rings, both groups are providing
comparable yields. To study the steric effect, orthoꢀ, metaꢀ and
OH
O
H
O
O
Me
O
Me
O
O
H
O
Me
O
Me
OMe
H
H
O
O
Me
OSO2Ph
Me
Me
HO
aspergillide C
Me
kendomycin
laulimolide
Figure 1. Structures of natural products containing pyran ring
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CHO
2i
F
paraꢀchlorobenazaldehydes (entries 4ꢀ6) were reacted with
alcohol 1, but the effect is not noticeable. On the other hand,
highly sterically hindered 2,6ꢀdichlorobenzaldehyde (entry 7) and
4ꢀchloroꢀ3ꢀnitrobenzaldehyde (entry 12) gave low yields. 4ꢀ
Methoxybenzaldehyde was found to be decomposed under these
reaction conditions. Reaction of 2p gave two inseparable
9
70
O
F
3i
OTf
5
CF3
CHO
1
10
65
O
diastereomers with a ratio of 2:1, which was determined by H
F3C
2j
NMR.
3j
OTf
O
10
NO2
Table 1. Synthesis of dihydropyransa
CHO
11
12
70
2k
NO2
O
O
R
TfOH / CH2Cl2
rt / 12h
3k
+
OTf
R
H
OH
O2N
Cl
CHO
Cl
3
2
61
1
OTf
O
NO2
2l
Entry
Aldehyde 2
Product 3
Yield
(%)b
3l
CO2Me
72
OTf
CHO
1
92
CHO
O
2a
O
13
MeO2C
2m
3a
Me
OTf
OTf
O
3m
CHO
2b
14
CHO
2
3
80
O
73
Me
2n
3b
3n
OTf
OTf
O
OMe
CHO
67
CHO
d
O
15
2o
2c
MeO
3o
OTf
3c
3d
OTf
O
Cl
16
CHO
2p
64b
CHO
4
5
O
72
74
2d
Cl
OTf
3p
OTf
O
aYields refer to isolated yield. Compounds are characterized by IR, NMR
and mass spectrometry.
decomposed. bTwo inseparable
diastereomeric mixture with a ratio of 2:1 determined by 1H NMR.
Cl
CHO
d
=
Cl
Cl
2e
3e
OTf
O
15
6
CHO
75
2f
Cl
3f
OTf
Cl
Cl
20
CHO
Cl
O
7
8
60
78
Cl
2g
3g
OTf
O
25 Figure 2. Xꢀray crystallographic structure of 3n
Br
CHO
Br
2h
The mechanism of the reaction can be explained as follows. The
acidic proton activates the aldehyde for nucleophilic attack by
30 homopropargylic alcohols to form oxocarbenium ion 5, which
3h
OTf
2
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after Prins cyclization generates carbocation 6. The carbocation 6
4ꢀaryl tetrahydropyrans are prepared by PrinsꢀFriedelꢀCrafts
is then attacked by triflate ion to give dihydropyran 3 (Scheme 1). 60 reactions.23b,c,25 The major drawback of the existing methods is
that the electron deficient aromatic rings cannot participate in this
reaction. Therefore, use of triflates 3 as an arylating unit via
OTf
5
10
15
Suzuki coupling would be a better alternative for introduction of
various aryl groups including both electron donating and electron
65 withdrawing groups. Thus the reaction of 3a with different aryl
and heteroaryl boronic acids 7aꢀf under Suzuki coupling
conditions afforded 4ꢀarylꢀ dihydropyrans 8aꢀf in good yields
(Table 2). Similarly, Heck, Stille and Sonogashira coupling of 3a
produce corresponding coupling products 9, 10 and 11,
70 respectively, in excellent yields (Schemes 2ꢀ4).
H+
Prins
Cyclization
O
OH2
2
R
H
R
R
O
O
R
O
6
HO
5
4
1
OTf
O
R
Scheme 2. Heck coupling reaction
3
Scheme 1. Mechanism of the reaction
75
The reaction is further utilized for the synthesis of 4ꢀarylated
dihydropyrans. It may be noted that 4ꢀarylated tetrahydropyrans
20 are found in many biologically active natural products.1 Generally
Table 2. Suzuki coupling reaction
80
Scheme 3. Stille coupling reaction
ArB(OH)2
7
O
O
PdCl2, Ph3P,
25
30
35
40
45
50
55
Na2CO3, THF
400C, 1 h
85
Ar
8
OTf
3
yield (%)a
95
boronic acid 7
Sl. No.
1
product 8
B(OH)2
7a
O
8a
8b
8c
90 Scheme 4. Sonogashira coupling reaction
B(OH)2
93
94
O
7b
2
O
Cl
O
95
PdCl2, Ph3P, CuI
11
OTf
Et3N, DMF
Cl
O
B(OH)2
3a
800C, 2h, 95%
3
7c
F
100 Conclusions
F
O
B(OH)2
In conclusion, we have developed one pot, three component, mild
91
and
efficient
method
for
the
synthesis
of
4ꢀ
4
5
6
8d
7d
trifluoromethanesulfonate substituted dihydropyrans via Prins
105 cyclization reaction in good yields. The reaction is compatible
with a wide range of functional groups such as ester, ether, nitro,
and bromo. The aspect of this reaction is that it introduces
trifluoromethanesulfonate group at 4ꢀposition of the
dihydropyrans, which can be used for subsequent coupling
110 reactions such as Suzuki, Heck, Stille and Sonogashira coupling
reactions.
NO2
NO2
B(OH)2
O
90
92
MeO
8e
7e
OMe
O
S
Experimental
B(OH)2
7f
8f
S
115 General Information: All the reagents were of reagent grade
aYields refer to isolated yield. Compounds are caharacterized by IR, NMR spectroscopy and mass
spectrometry.
(AR grade) and were used as purchased without further
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purification. Silica gel (60ꢀ120 mesh size) was used for column
4.0 Hz, 1 H), 5.22 (d, J = 4.0 Hz, 1 H), 5.91 (s, 1 H), 7.18 (d, J =
chromatography. Reactions were monitored by TLC on silica gel 60 7.2 Hz, 2 H), 7.23 (d, J = 7.2 Hz, 2 H); 13C NMR (150 MHz,
GF254 (0.25 mm). Melting points were recorded in an open
capillary tube and are uncorrected. Fourier transformꢀinfra red
(FTꢀIR) spectra were recorded as neat liquid or KBr pellets.
CDCl3) δ 21.3, 28.5, 62.9, 75.5, 118.7 (q, J = 318.0 Hz), 120.3,
127.7, 129.6, 136.0, 138.8, 146.8; 19F NMR (376 MHz,
CDCl3/TFA) δ 1.99 (s, ꢀF); IR (KBr, neat) 2926, 2866, 1689,
1420, 1349, 1212, 1142, 1071, 899, 816 cmꢀ1; HRMS (ESI) calcd.
5
NMR spectra were recorded in CDCl3 with tetramethylsilane as
1
the internal standard for H (600 MHz, 400 MHz) or 13C (150 65 for C13H14F3O4S (M + H)+ 323.0559, found 323.0565.
MHz, 100 MHz) NMR. Chemical shifts (δ) are reported in ppm
and spinꢀspin coupling constants (J) are given in Hz. HRMS
10 spectra were recorded using QꢀTOF mass spectrometer.
6-(2-Chlorophenyl)-3,6-dihydro-2H-pyran-4-yl
trifluoro-
methanesulfonate (3d). Colourless oil; Rf (hexane/ EtOAc 50:1)
1
0.2; yield 246 mg, 72%; H NMR (400 MHz, CDCl3) δ 2.38 (dd,
General
Procedure
for
the
formation
of
4- 70 J = 12.0 and 4.0 Hz, 1 H), 2.70ꢀ2.76 (m, 1 H), 3.88 (ddd, J =
12.0, 8.0 and 4.0 Hz, 1 H), 4.16 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1
H), 5.70 (d, J = 4.0 Hz, 1 H), 5.90 (s, 1 H), 7.24ꢀ7.29 (m, 2 H),
7.39 (dd, J = 7.2 and 4.0 Hz, 1 H), 7.45 (d, J = 7.2 Hz, 1 H); 13C
NMR (150 MHz, CDCl3) δ 28.4, 63.4, 72.4, 117.4 (q, J = 319.5
trifluoromethanesulfonate 3,6-dihydropyan:
To a stirring solution of aldehyde (1.0 equiv) and 3ꢀbutynꢀ1ꢀol
15 (1.5 equiv) in dry dichloromethane (5.0 mL) was added triflic
acid (1.2 equiv) dropwise at 0 0C. The reaction mixture was
brought to room temperature and stirred for a specific time. The 75 Hz), 119.7, 127.3, 128.9, 129.9, 130.0, 133.1, 136.4, 147.1; 19F
progress of the reaction was monitored by TLC using ethyl
acetate and hexane as eluents. After completion of the reaction,
20 the reaction mixture was treated with saturated sodium
bicarbonate solution (5.0 mL). The product was extracted with
CH2Cl2 (2 x 10.0 mL) and washed with brine. Organic layer was
separated and dried over anhydrous Na2SO4 and evaporated using
rotary evaporator to obtain the crude product. The crude product
25 was purified by silica gel column chromatography using ethyl
acetate and hexane as eluents to afford the cyclic compounds.
NMR (376 MHz, CDCl3/TFA) δ 2.01 (s, ꢀF); IR (KBr, neat)
2928, 2872, 1690, 1420, 1219, 1142, 1065, 764 cmꢀ1; HRMS
(ESI) calcd. for C12H11ClF3O4S (M + H)+ 343.0013, found
343.0010.
80
6-(3-Chlorophenyl)-3,6-dihydro-2H-pyran-4-yl
trifluoro-
methanesulfonate (3e). Colourless oil; Rf (hexane/ EtOAc 50:1)
1
0.2; yield 253 mg, 74%; H NMR (400 MHz, CDCl3) δ 2.41 (dd,
J = 12.0 and 4.0 Hz, 1 H), 2.66ꢀ2.73 (m, 1 H), 3.86 (ddd, J =
85 12.0, 8.0 and 4.0 Hz, 1 H), 4.11 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1
H), 5.24 (d, J = 4.0 Hz, 1 H), 5.90 (s, 1 H), 7.21ꢀ7.23 (m, 1 H),
7.31ꢀ7.32 (m, 2 H), 7.35 (d, J = 7.2 Hz, 1 H); 13C NMR (150
MHz, CDCl3) δ 28.4, 63.1, 75.0, 118.7 (q, J = 318.0 Hz), 119.7,
125.7, 127.9, 129.0, 130.2, 134.8, 141.1, 147.2; 19F NMR (376
Synthesis
of
6-phenyl-3,6-dihydro-2H-pyran-4-yl
trifluoromethanesulfonate (3a). To a stirring solution of
30 benzaldehyde (0.1 mL, 1 mmol) and 3ꢀbutynꢀ1ꢀol (0.11 mL, 1.5
mmol) in CH2Cl2 (5 mL) was added TfOH (0.1 mL, 1.2 mmol)
dropwise at 00C. The reaction mixture was brought to room 90 MHz, CDCl3/TFA) δ 2.08 (s, ꢀF); IR (KBr, neat) 2928, 2870,
temperature and stirred for 12 h. The progress of the reaction
was monitored by TLC using ethyl acetate and hexane as eluents.
35 After completion of the reaction, CH2Cl2 (10 mL) was added and
the reaction mixture was washed with saturated sodium
1689, 1421, 1214, 1142, 1073, 875 cmꢀ1; HRMS (ESI) calcd. for
C12H11ClF3O4S (M + H)+ 343.0013, found 343.0035.
6-(4-Chlorophenyl)-3,6-dihydro-2H-pyran-4-yl
trifluoro-
bicarbonatesolution and brine solution. The organic layer was 95 methanesulfonate (3f). Colourless oil; Rf (hexane/ EtOAc 50:1)
1
separated and dried over anhydrous Na2SO4 and evaporated using
rotary evaporator to leave the crude product which was purified
40 by column chromatography over silica gel using ethyl acetate and
hexane as eluents to give 6ꢀphenylꢀ3,6ꢀdihydroꢀ2Hꢀpyranꢀ4ꢀyl
0.2; yield 256 mg, 75%; H NMR (400 MHz, CDCl3) δ 2.42 (dd,
J = 12.0 and 6.0 Hz, 1 H), 2.67ꢀ2.74 (m, 1 H), 3.86 (ddd, J =
12.0, 8.0 and 4.0 Hz, 1 H), 4.16 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1
H), 5.25 (d, J = 6.0 Hz, 1 H), 5.89 (s, 1 H), 7.28 (d, J = 7.2 Hz, 2
trifluoromethanesulfonate 3a; colourless oil; Rf (hexane/ EtOAc 100 H), 7.36 (d, J = 7.2 Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ
1
50:1) 0.20; yield 292 mg, 92%; H NMR (400 MHz, CDCl3) δ
2.05 (dd, J = 16.0 and 6.0 Hz, 1 H), 2.68ꢀ2.73 (m, 1 H), 3.86
45 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H), 4.11 (ddd, J = 12.0, 8.0 and
4.0 Hz, 1 H), 5.26 (d, J = 4.0 Hz, 1 H), 5.93 (s, 1 H), 7.34ꢀ7.38
28.3, 63.0, 74.9, 115.4 (q, J = 318.0 Hz), 120.2, 129.0 (2C),
134.6, 137.6, 147.1; 19F NMR (376 MHz, CDCl3/TFA) δ 1.97 (s,
ꢀF); IR (KBr, neat) 2929, 2869, 1692, 1421, 1213, 1148, 1091,
1066, 900, 765, 613 cmꢀ1; HRMS (ESI) calcd. for C12H11ClF3O4S
(m, 5 H); 13C NMR (100 MHz, CDCl3) δ 28.5, 63.1, 75.8, 118.7 105 (M + H)+ 343.0013, found 343.0017.
(q, J = 318.0 Hz), 120.2, 127.8, 128.9, 128.9, 139.0, 146.9; 19F
NMR (376 MHz, CDCl3/TFA) δ 2.03 (s, ꢀF); IR (KBr, neat)
50 2929, 2869, 1690, 1455, 1422, 1351, 1246, 1141, 1029, 894, 762
cmꢀ1; HRMS (ESI) calcd. for C12H12F3O4S (M + H)+ 309.0403,
found 309.0408.
6-(2,6-Dichlorophenyl)-3,6-dihydro-2H-pyran-4-yl trifluoro-
methanesulfonate (3g). Colourless oil; Rf (hexane/ EtOAc 50:1)
0.19; yield 225mg, 60%; 1H NMR (400 MHz, CDCl3) δ 2.38 (dd,
110 J = 12.0 and 4.0 Hz, 1 H), 2.81ꢀ2.91 (m, 1 H), 3.88 (ddd, J =
12.0, 8.0 and 4.0 Hz, 1 H), 4.24 (dd, J = 12.0 and 4.0 Hz, 1 H),
5.78 (s, 1 H), 5.97 (s, 1 H), 7.17 (t, J = 7.2 Hz, 1 H), 7.31 (d, J =
8.0 Hz, 2 H); 13C NMR (150 MHz, CDCl3) δ 28.1, 65.2, 72.7,
118.6 (q, J = 318.0 Hz), 119.7, 129.6, 130.5, 133.1, 136.1, 146.9;
6-(p-Tolyl)-3,6-dihydro-2H-pyran-4-yl
trifluoromethane-
55 sulfonate (3b). Colourless oil; Rf (hexane/ EtOAc 50:1) 0.21;
1
yield 257mg, 80%; H NMR (400 MHz, CDCl3) δ 2.34 (s, 3 H),
2.40 (dd, J = 12.0 and 4.0 Hz, 1 H), 2.65ꢀ2.70 (m, 1 H), 3.83 115 19F NMR (376 MHz, CDCl3/TFA) δ 1.91 (s, ꢀF); IR (KBr, neat)
(ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H), 4.11 (ddd, J = 12.0, 8.0 and
2923, 2857, 1659, 1437, 1219, 1119, 1052, 775 cmꢀ1; HRMS
4
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1
(ESI) calcd. for C12H10Cl2F3O4S (M + H)+ 376.9623, found
376.9627.
50:1) 0.25; yield 236mg, 61%; H NMR (600 MHz, CDCl3) δ
60 2.44 (dd, J = 18.0 and 6.0 Hz, 1 H), 2.70ꢀ2.76 (m, 1 H), 3.90
(ddd, J = 12.0, 6.0 and 6.0 Hz, 1 H), 4.13 (ddd, J = 12.0, 6.0 and
6.0 Hz, 1 H), 5.33 (d, J = 4.0 Hz, 1 H), 5.90 (s, 1 H), 7.51 (d, J =
7.2 Hz, 1 H), 7.57 (d, J = 7.2 Hz, 1 H), 7.89 (d, J = 7.2 Hz, 1 H);
13C NMR (150 MHz, CDCl3) δ 28.3, 63.3, 74.0, 118.6, 118.7 (q,
6-(3-Bromophenyl)-3,6-dihydro-2H-pyran-4-yl
trifluoro-
5
methanesulfonate (3h). Colourless oil; Rf (hexane/ EtOAc 50:1)
0.18; yield 301mg, 78%; 1H NMR (400 MHz, CDCl3) δ 2.42 (dd,
J = 12.0 and 4.0 Hz, 1 H), 2.66ꢀ2.74 (m, 1 H), 3.87 (ddd, J = 65 J = 318.0 Hz), 124.6, 127.3, 131.9, 132.5, 139.8, 147.8, 148.2;
12.0, 8.0 and 4.0 Hz, 1 H), 4.11 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1
H), 5.24 (d, J = 4.0 Hz, 1 H), 5.90 (s, 1 H), 7.25 (d, J = 8.0 Hz, 2
19F NMR (376 MHz, CDCl3/TFA) δ 2.1 (s, ꢀF); IR (KBr, neat)
2927, 2873, 1690, 1539, 1421, 1353, 1214, 1141, 1073, 888, 792
cmꢀ1; HRMS (ESI) calcd. for C12H9F3NO6SNa (M + Na)+
409.9689, found 409.9691.
10 H), 7.46ꢀ7.51 (m, 2 H); 13C NMR (150 MHz, CDCl3) δ 28.4,
63.1, 74.9, 118.6 (q, J = 319.5 Hz), 119.7, 122.9, 126.2, 130.5,
130.8, 131.9, 141.4, 147.2; 19F NMR (376 MHz, CDCl3/TFA) δ
2.04 (s, ꢀF); IR (KBr, neat) 2871, 1690, 1420, 1213, 1141, 1072,
784 cmꢀ1; HRMS (ESI) calcd. for C12H11BrF3O4S (M + H)+
15 386.9508, found 386.9520.
70
Methyl 4-(4-(((trifluoromethyl)sulfonyl)oxy)-3,6-dihydro-2H-
pyran-2-yl)benzoate (3m). Colourless oil; Rf (hexane/ EtOAc
1
50:1) 0.23; yield 263 mg, 72%; H NMR (600 MHz, CDCl3) δ
2.41 (dd, J = 16.0 and 6.0 Hz, 1 H), 2.68ꢀ2.74 (m, 1 H), 3.88
6-(4-Fluorophenyl)-3,6-dihydro-2H-pyran-4-yl
trifluoro- 75 (ddd, J = 12.0, 6.0 and 6.0 Hz, 1 H), 3.91 (s, 3 H), 4.12 (ddd, J =
methanesulfonate (3i). Colourless oil; Rf (hexane/ EtOAc 50:1)
0.19; yield 228mg, 70%; 1H NMR (600 MHz, CDCl3) δ 2.41 (dd,
20 J = 12.0 and 6.0 Hz, 1 H), 2.67ꢀ2.74 (m, 1 H), 3.86 (ddd, J =
12.0, 6.0 and 6.0 Hz, 1 H), 4.11 (ddd, J = 12.0, 6.0 and 6.0 Hz, 1
12.0, 6.0 and 6.0 Hz, 1 H), 5.31 (s, 1 H), 5.91 (s, 1 H), 7.42 (d, J
= 7.2 Hz, 2 H), 8.04 (d, J = 7.2 Hz, 2 H); 13C NMR (150 MHz,
CDCl3) δ 28.4, 52.4, 63.2, 75.2, 118.6 (q, J = 319.5 Hz), 119.7,
127.5, 130.2, 130.6, 144.0, 147.1, 166.8; 19F NMR (376 MHz,
H), 5.25 (d, J = 6.0 Hz, 1 H), 5.90 (s, 1 H), 7.07 (d, J = 8.0 Hz, 2 80 CDCl3/TFA) δ 2.07 (s, ꢀF); IR (KBr, neat) 2925, 2850, 1725,
H), 7.32 (d, J = 8.0 Hz, 2 H); 13C NMR (150 MHz, CDCl3) δ
28.4, 63.0, 75.0, 115.7, 118.7 (q, J = 318.0 Hz), 119.9, 129.4,
25 134.9, 147.0, 163.0 (q, J = 246.0 Hz); 19F NMR (376 MHz,
CDCl3/TFA) δ 2.06 (s, ꢀF); IR (KBr, neat) 2925, 2869, 1690,
1690, 1418, 1282, 1213, 1142, 1113, 1072, 860, 771 cmꢀ1; HRMS
(ESI) calcd. for C14H14F3O6S (M + H)+ 367.0458, found
367.0465.
1421, 1219, 1141, 1071, 897, 775 cmꢀ1; HRMS (ESI) calcd. for 85 6-(Naphthalen-2-yl)-3,6-dihydro-2H-pyran-4-yl
trifluoro-
C12H11F4O4S (M + H)+ 327.0309, found 327.0313.
methanesulfonate (3n). Colourless solid; mp 71ꢀ73 oC Rf
1
(hexane/ EtOAc 50:1) 0.20; yield 261mg, 73%; H NMR (600
30 6-(4-(Trifluoromethyl)phenyl)-3,6-dihydro-2H-pyran-4-yl
trifluoromethanesulfonate (3j). Pale yellow oil; Rf (hexane/
MHz, CDCl3) δ 2.42 (dd, J = 12.0 and 4.0 Hz, 1 H), 2.67ꢀ2.83
(m, 1 H), 3.86 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H), 4.10 (ddd, J =
EtOAc 50:1) 0.20; yield 244mg, 65%; 1H NMR (600 MHz, 90 12.0, 8.0 and 4.0 Hz, 1 H), 5.39 (d, J = 4.0 Hz, 1 H), 5.99 (s, 1
CDCl3) δ 2.42 (dd, J = 18.0 and 6.0 Hz, 1 H), 2.69ꢀ2.76 (m, 1 H),
3.90 (ddd, J = 12.0, 6.0 and 6.0 Hz, 1 H), 4.14 (ddd, J = 12.0, 6.0
35 and 6.0 Hz, 1 H), 5.33 (d, J = 6.0 Hz, 1 H), 5.92 (s, 1 H), 7.48 (d,
J = 8.0 Hz, 2 H), 7.66 (d, J = 8.0 Hz, 2 H); 13C NMR (150 MHz,
H), 7.43 (d, J = 8.0 Hz, 1 H), 7.47ꢀ7.50 (m, 2 H), 7.77 (s, 1 H),
7.81ꢀ7.85 (m, 3 H); 13C NMR (150 MHz, CDCl3) δ 28.5, 62.9,
75.7, 118.7 (q, J = 318.0 Hz), 120.1, 125.2, 126.5, 126.6, 127.0,
127.9, 128.3, 128.9, 133.3, 133.5, 136.4, 147.0; 19F NMR (376
CDCl3) δ 28.4, 63.3, 75.1, 118.7 (q, J = 319.5 Hz), 119.5, 121.9, 95 MHz, CDCl3/TFA) δ 2.04 (s, ꢀF); IR (KBr, neat) 2976, 2868,
124.1 (q, J = 270.0 Hz), 126.0, 128.0, 130.3, 143.0, 147.3; 19F
NMR (376 MHz, CDCl3/TFA) δ 2.20 (s, ꢀF), 13.27 (s, ꢀF); IR
40 (KBr, neat) 2928, 2872, 1622, 1421, 1327, 1216, 1130, 1069,
858, 792 cmꢀ1; HRMS (ESI) calcd. for C13H11F6O4S (M + H)+
377.0277, found 377.0249.
1689, 1464, 1422, 1244, 1114, 1058, 886, 757 cmꢀ1; HRMS (ESI)
calcd. for C16H14F3O4S (M + H)+ 359.0559, found 359.0564.
6-Isobutyl-3,6-dihydro-2H-pyran-4-yl
trifluoromethane-
100 sulfonate (3o). Colourless oil; Rf (hexane/ EtOAc 50:1) 0.20;
1
yield 193mg, 67%; H NMR (600 MHz, CDCl3) δ 0.93 (s, 3 H),
6-(2-Nitrophenyl)-3,6-dihydro-2H-pyran-4-yl
trifluoro-
0.94 (s, 3 H), 1.27ꢀ1.32 (m, 1 H), 1.55ꢀ1.60 (m, 1 H), 1.79ꢀ1.87
(m, 1 H), 2.26 (dd, J = 12.0 and 4.0 Hz, 1 H), 2.58ꢀ2.64 (m, 1 H),
3.71 (ddd, J = 12.0, 6.0 and 6.0 Hz, 1 H), 4.09 (ddd, J = 12.0, 6.0
45 methanesulfonate (3k). Yellow oil; Rf (hexane/ EtOAc 50:1)
0.25; yield 247mg, 70%; 1H NMR (600 MHz, CDCl3) δ 2.39 (dd,
J = 18.0 and 6.0 Hz, 1 H), 2.79ꢀ2.85 (m, 1 H), 3.91 (ddd, J = 105 and 6.0 Hz, 1 H), 4.27 (d, J = 6.0 Hz, 1 H), 5.72 (s, 1 H); 13C
12.0, 6.0 and 6.0 Hz, 1 H), 4.22 (ddd, J = 12.0, 6.0 and 6.0 Hz, 1
H), 5.86 (d, J = 6.0 Hz, 1 H), 6.02 (s, 1 H), 7.50 (t, J = 7.2 Hz, 1
50 H), 7.66 (d, J = 7.2 Hz, 1 H), 7.73 (d, J = 7.2 Hz, 1 H), 7.98 (d, J
= 7.2 Hz, 1 H); 13C NMR (150 MHz, CDCl3) δ 28.3, 63.9, 71.4,
NMR (150 MHz, CDCl3) δ 22.1, 23.3, 24.5, 28.6, 43.8, 63.2,
71.9, 117.6 (q, J = 318.0 Hz), 121.2, 146.4; 19F NMR (376 MHz,
CDCl3/TFA) δ 2.05 (s, ꢀF); IR (KBr, neat) 2960, 2872, 1690,
1442, 1211, 1143, 1072, 884, 614 cmꢀ1; HRMS (ESI) calcd. for
118.6 (q, J = 318.0 Hz), 119.9, 124.8, 129.3, 129.4, 133.9, 134.6, 110 C10H16F3O4S (M + H)+ 289.0721, found 289.0715.
147.1, 148.2; 19F NMR (376 MHz, CDCl3/TFA) δ 1.97 (s, ꢀF); IR
(KBr, neat) 2929, 2873, 1689, 1531, 1419, 1353, 1211, 1141,
55 1073, 901, 789, 751 cmꢀ1; HRMS (ESI) calcd. for C12H11F3NO6S
(M + H)+ 354.0259, found 354.0259.
6-(4-Chloro-3-nitrophenyl)-3,6-dihydro-2H-pyran-4-yl
trifluoromethanesulfonate (3l). Yellow oil; Rf (hexane/ EtOAc
6-(1-Phenylethyl)-3,6-dihydro-2H-pyran-4-yl
trifluoro-
methanesulfonate (diastereomeric mixture, 2:1, 3p).
Colourless oil; Rf (hexane/ EtOAc 50:1) 0.20; yield 215mg, 64%;
115 1H NMR (400 MHz, CDCl3) δ 1.30 (d, J = 4.0 Hz, 3 H, minor),
1.35 (d, J = 8.0 Hz, 3 H, major), 2.07ꢀ2.12 (m, 1 H, minor), 2.16ꢀ
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2.24 (m, 1 H, major), 2.56ꢀ2.64 (m, 1 H), 2.82ꢀ2.89 (m, 1 H,
major), 3.08ꢀ3.15 (m, 1 H, minor), 3.62ꢀ3.71 (m, 1 H), 4.09ꢀ4.13 60 H), 2.68ꢀ2.77 (m, 1 H), 3.92 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H),
1H NMR (400 MHz, CDCl3) δ 2.45 (dd, J = 16.0 and 4.0 Hz, 1
(m, 1 H), 4.24ꢀ4.26 (m, 1 H, major), 4.36ꢀ4.37 (m, 1 H, minor),
5.54 (s, 1 H, major), 5.68 (s, 1 H, minor), 7.20ꢀ7.26 (m, 3 H),
7.29ꢀ7.35 (m, 2 H); 13C NMR (150 MHz, CDCl3) δ 15.0, 17.0,
28.4, 43.6, 44.7, 63.4, 63.8, 78.1, 78.2, 118.6 (q, J = 319.5 Hz),
4.19 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H), 5.30 (d, J = 4.0 Hz, 1
H), 6.16 (s, 1 H), 7.03 (t, J = 8.0 Hz, 2 H), 7.29ꢀ7.43 (m, 7 H);
13C NMR (100 MHz, CDCl3) δ 27.3, 63.6, 76.9, 115.5 (d, J =
21.0 Hz), 125.4, 126.3 (d, J = 8.0 Hz), 127.8, 128.2, 128.7, 134.1,
5
119.7, 126.9, 127.0, 128.0, 128.1, 128.6, 128.7, 142.1, 142.9, 65 136.3 (d, J = 3.3 Hz), 141.3, 162.5 (d, J = 245.1 Hz); 19F NMR
147.0, 147.3; 19F NMR (376 MHz, CDCl3/TFA) δ 1.9 (s, ꢀF); IR
(KBr, neat) 2972, 2873, 1690, 1420, 1213, 1143, 1073, 891, 763
(376 MHz, CDCl3/TFA) δ ꢀ39.2 (s, ꢀF); IR (KBr, neat) 2925,
2854, 1601, 1451, 1275, 1231, 1160, 1071, 836, 700 cmꢀ1; HRMS
(ESI) calcd. for C17H16FO (M + H)+ 255.1180, found 255.1185.
10 cmꢀ1; HRMS (ESI) calcd. for C14H16F3O4S (M + H)+ 337.0716,
found 337.0722.
4-(3-Nitrophenyl)-6-phenyl-3,6-dihydro-2H-pyran
(8d).
70 Yellow oil; Rf (hexane/ EtOAc 50:1) 0.30; yield 255 mg, 91%;
1H NMR (400 MHz, CDCl3) δ 2.51 (dd, J = 16.0 and 4.0 Hz, 1
H), 2.76ꢀ2.85 (m, 1 H), 3.96 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H),
4.25 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H), 5.34 (d, J = 4.0 Hz, 1
H), 6.38 (s, 1 H), 7.31ꢀ7.43 (m, 5 H), 7.52 (t, J = 8.0 Hz, 1 H),
General procedure of Suzuki coupling reaction.
To a solution of 3 (1.0 mmol) in THF (4.0 mL) were added PPh3
15 (5 mol %), PdCl2 (5 mol %), boronic acid 7 (1.56 mmol) and 2M
aqueous solution of Na2CO3 (2.0 mL) under inert atmosphere.
The reaction mixture was stirred at 40 0C for 1hr. Then water was 75 7.76 (t, J = 8.0 Hz, 1 H), 8.13 (d, J = 8.0 Hz, 1 H), 8.28 (s, 1 H);
added to reaction mixture and extracted with EtOAc (3×10 mL).
Combined organic layer was dried and concentrated under
20 reduced pressure. Residue obtained was purified by silica gel
column chromatography using EtOAc/hexane as eluent to furnish
the compound 8.
13C NMR (100 MHz, CDCl3) δ 27.0, 63.4, 76.8, 119.9, 122.4,
127.6, 128.4, 128.8, 129.6, 130.9, 133.1, 140.8, 141.8, 148.7; IR
(KBr, neat) 2924, 2855, 1528, 1453, 1349, 1269, 1121, 1063,
892, 737 cmꢀ1; HRMS (ESI) calcd. for C17H16NO3 (M + H)+
80 282.1125, found 282.1130.
Synthesis of 4,6-Diphenyl-3,6-dihydro-2H-pyran (8a). To a
Synthesis of 4-(4-methoxyphenyl)-6-phenyl-3,6-dihydro-2H-
pyran (8e). A mixture of 3a (308 mg, 1.0 mmol), aqueous
sodium carbonate (1.4 mL, 2.80 mmol), lithium chloride (125
25 solution
of
3,6ꢀdihydroꢀ2ꢀphenylꢀ2Hꢀpyranꢀ4ꢀyl
trifluoromethanesulfonate 3a (308 mg, 1 mmol) in THF (4.0 mL)
were added PPh3(14 mg, 5 mol %), PdCl2 (9 mg, 5 mol%), phenyl 85 mg, 2.98 mmol), Pd(Ph3P)4 (23 mg, 0.02 mmol), 4ꢀ
boronic acid 7a (183 mg, 1.56 mmol) and 2M aqueous solution of
methoxyphenylboronic acid (166 mg, 1.09 mmol), and THF (5
mL) was refluxed for 3 h. After completion of the reaction the
solvent was removed by evaporation; water was added and the
mixture was extracted with ethyl acetate (2x10 mL). Combined
Na2CO3 (2.0 mL) under inert atmosphere. The reaction mixture
o
30 was stirred at 40 C for 1h. Then water was added to reaction
mixture and extracted with EtOAc (3×10 mL). Combined organic
layer was dried and concentrated under reduced pressure. Residue 90 organic layer was dried and concentrated under reduced pressure.
obtained was purified by silica gel column chromatography using
EtOAc/hexane as eluent to furnish the 2,4ꢀdiphenylꢀ3,6ꢀdihydroꢀ
35 2Hꢀpyran as a yellow oil; Rf (hexane/ EtOAc 50:1) 0.3; yield 224
The product was purified by column chromatography on silica
gel (ethyl acetate/hexane, 1/4) to give 8e as a pale yellow oil; Rf
1
(hexane/ EtOAc 50:1) 0.40; yield 239 mg, 90%; H NMR (600
1
mg, 95%; H NMR (400 MHz, CDCl3) δ 2.49 (dd, J = 12.0 and
MHz, CDCl3) δ 2.51 (dd, J = 16.0 and 6.0 Hz, 1 H), 2.68ꢀ2.74
4.0 Hz, 1 H), 2.71ꢀ2.80 (m, 1 H), 2.92 (ddd, J = 12.0, 8.0 and 4.0 95 (m, 1 H), 3.80 (s, 3 H), 3.91 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H),
Hz, 1 H), 4.19 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H), 5.31 (d, J =
4.0 Hz, 1 H), 6.22 (s, 1 H), 7.27ꢀ7.39 (m, 6 H), 7.41ꢀ7.45 (m, 4
40 H); 13C NMR (100 MHz, CDCl3) δ 27.2, 63.6, 76.9, 125.1, 125.5,
127.7, 127.8, 128.2, 128.6, 128.7, 135.0. 140.2, 141.5; IR (KBr,
4.17 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H), 5.29 (d, J = 4.0 Hz, 1
H), 6.12 (s, 1 H), 6.88 (d, J = 8.0 Hz, 2 H), 7.30 (t, J = 8.0 Hz, 1
H), 7.34ꢀ7.38 (m, 4 H), 7.42 (d, J = 8.0 Hz, 2 H); 13C NMR (150
MHz, CDCl3) δ 27.3, 55.5, 63.7, 76.9, 114.0, 123.8, 126.2, 127.8,
neat) 2924, 2853, 1600, 1493, 1263, 1120, 1029, 771 cmꢀ1; 100 128.1, 128.7, 132.8, 134.4, 141.7, 159.4; IR (KBr, neat) 2957,
HRMS (ESI) calcd. for C17H17O (M + H)+ 237.1274, found
237.1277.
2836, 1607, 1456, 1309, 1248, 1180, 1062, 1034, 832, 761, 700
cmꢀ1; HRMS (ESI) calcd. for C18H19O2 (M + H)+ 267.1385, found
267.1385.
45
4-(4-Chlorophenyl)-6-phenyl-3,6-dihydro-2H-pyran
(8b).
Pale yellow oil; Rf (hexane/ EtOAc 50:1) 0.28; yield 251 mg, 105 6-Phenyl-4-(thiophen-2-yl)-3,6-dihydro-2H-pyran (8f). Yellow
1
93%; H NMR (400 MHz, CDCl3) δ 2.44 (dd, J = 12.0 and 4.0
Hz, 1 H), 2.67ꢀ2.76 (m, 1 H), 3.91 (ddd, J = 12.0, 8.0 and 4.0 Hz,
oil; Rf (hexane/ EtOAc 50:1) 0.30; yield 222 mg, 92%; 1H NMR
(400 MHz, CDCl3) δ 2.49 (dd, J = 16.0 and 4.0 Hz, 1 H), 2.71ꢀ
2.78 (m, 1 H), 3.90 (ddd, J = 16.0, 8.0 and 4.0 Hz, 1 H), 4.15
(ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H), 5.28 (d, J = 4.0 Hz, 1 H),
50 1 H), 4.19 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H), 5.29 (d, J = 4.0
Hz, 1 H), 6.20 (s, 1 H), 7.29ꢀ7.42 (m, 9 H); 13C NMR (100 MHz,
CDCl3) δ 27.2, 63.5, 76.8, 126.1, 126.4, 127.7, 128.2, 128.8 (2C), 110 6.20 (s, 1 H), 6.99 (t, J = 8.0 Hz, 1 H), 7.03 (d, J = 8.0 Hz, 1 H),
133.5, 134.0, 138.6. 141.2; IR (KBr, neat) 2924, 2853, 1598,
1493, 1368, 1177, 1074, 762 cmꢀ1; HRMS (ESI) calcd. for
55 C17H16ClO (M + H)+ 271.0884, found 271.0886.
7.17 (d, J = 8.0 Hz, 1 H), 7.30 (d, J = 8.0 Hz, 1 H), 7.32ꢀ7.42 (m,
4 H); 13C NMR (100 MHz, CDCl3) δ 27.6, 63.3, 76.6, 122.5,
124.1, 127.5, 127.8, 128.2, 128.7, 129.7, 141.1, 144.8; IR (KBr,
neat) 2924, 2854, 1639, 1453, 1361, 1263, 1116, 1062, 879, 698
4-(4-Fluorophenyl)-6-phenyl-3,6-dihydro-2H-pyran (8c). Pale 115 cmꢀ1; HRMS (ESI) calcd. for C15H15OS (M + H)+ 243.0844,
yellow oil; Rf (hexane/ EtOAc 50:1) 0.25; yield 238 mg, 94%;
found 243.0851.
6
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(E)-6-Phenyl-4-styryl-3,6-dihydro-2H-pyran (9). To a solution
2.53ꢀ2.62 (m, 1 H), 3.83 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H),
of 3 (308 mg, 1.0 mmol) in DMF (10 mL) were added Pd(OAc)2 60 4.06 (ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H), 5.23 (d, J = 4.0 Hz, 1
(11 mg, 5 mol%) and AcOK (196 mg, 2 mmol) under inert
atmosphere. The reaction mixture was stirred at 60 0C for
overnight. Then water was added to reaction mixture and
extracted with EtOAc (3×10 mL). Combined organic layer was
H), 6.25 (s, 1 H), 7.28ꢀ7.32 (m, 4 H), 7.33ꢀ7.40 (m, 4 H), 7.42ꢀ
7.45 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 29.2, 63.2, 76.6,
89.1, 89.2, 119.6, 123.3, 127.7, 128.3, 128.4, 128.5, 128.8, 131.7,
135.2, 140.6; IR (KBr, neat) 2919, 2850, 1597, 1490, 1450, 1253,
5
dried and concentrated under reduced pressure. Residue obtained 65 1120, 1062, 756, 699 cmꢀ1; HRMS (ESI) calcd. for C19H17O (M +
was purified by silica gel column chromatography using
H)+ 261.1274, found 261.1279.
EtOAc/Pet. ether as eluent to furnish the compound 9 as yellow
1
10 oil; Rf (hexane/ EtOAc 50:1) 0.35; yield 222 mg, 85%; H NMR
(400 MHz, CDCl3) δ 2.38 (dd, J = 12.0 and 4.0 Hz, 1 H), 2.53ꢀ
2.62 (m, 1 H), 3.87 (ddd, J = 16.0, 8.0 and 4.0 Hz, 1 H), 4.15
(ddd, J = 12.0, 8.0 and 4.0 Hz, 1 H), 5.27 (d, J = 4.0 Hz, 1 H),
5.92 (s, 1 H), 6.57 (d, J = 16.0 Hz, 1 H), 6.81 (d, J = 16.0 Hz, 1
15 H), 7.20ꢀ7.25 (m, 1 H), 7.30ꢀ7.43 (m, 9 H); 13C NMR (100 MHz,
CDCl3) δ 25.0, 63.4, 76.9, 126.5, 127.3, 127.6, 127.7, 128.2,
Acknowledgement
70
PG gratefully acknowledges Council of Scientific and Industrial
Research (CSIR), New Delhi for her fellowship. Authors are
grateful to Council of Scientific and Industrial Research (CSIR),
New Delhi, for financial support (Grant No. 02/0159/13/EMRꢀII).
128.7, 128.8, 130.2, 130.5, 134.2, 137.4, 141.3; IR (KBr, neat) 75 Authors are also thankful to Central Instrument Facility (CIF) of
2924, 2853, 1593, 1492, 1274, 1118, 1092, 1012, 830, 699 cmꢀ1;
HRMS (ESI) calcd. for C19H19O (M + H)+ 263.1430, found
20 263.1436.
IIT Guwahati for NMR and XRD facilities.
Notes and references
Synthesis of 4-allyl-6-phenyl-3,6-dihydro-2H-pyran (10). A
dried reaction tube was charged with triflate 3 (308 mg, 1mmol).
To this PPh3 (14 mg, 5 mol%), PdCl2 (9 mg, 5 mol %) was added
25 and reaction tube was evacuated. Then LiCl (126 mg, 3 mmol),
dry DMF (10 mL) and allyltributylstannane (397 mg, 1.21mmol)
80
aDepartment of Chemistry, Indian Institute of Technology
Guwahati, Guwahati, India. Fax: +91 361 2690762; Tel: +91
361 2582316; E-mail: asaikia@iitg.ernet.in
† Electronic Supplementary Information (ESI) available:
were added under nitrogen atmosphere. Reaction mixture was 85 [Experimental procedures, H, 13C and HRMS spectra of all new
1
0
heated at 80 C for 2 h. Reaction was quenched with saturated
NH4Cl solution and extracted with EtOAc (4×5 mL). Combined
30 organic layer was dried and concentrated under reduced pressure.
Residue obtained was purified by silica gel column
compounds]. See DOI: 10.1039/b000000x/
1 (a) X. Tian and S. D. Rychnovsky, Org. Lett., 2007, 9, 4955ꢀ
4958; (b) T. Washio, H. Nambu, M. Anada and S. Hashimoto,
chromatography using EtOAc/hexane as eluent to furnish 4ꢀallylꢀ 90 Tetrahedron: Asymmetry, 2007, 18, 2606ꢀ2612.
3,6ꢀdihydroꢀ2ꢀphenylꢀ2Hꢀpyran 10 (174 mg, 87%) as yellow oil;
Rf (hexane/ EtOAc 50:1) 0.35; yield 174 mg, 87%; 1H NMR (400
35 MHz, CDCl3) δ 1.98 (dd, J = 16.0 and 4.0 Hz, 1 H), 2.25ꢀ2.33
(m, 1 H), 2.80 (d, J = 8.0 Hz, 2 H), 3.78 (ddd, J = 12.0, 8.0 and
2 S. M. Ringel, R. C. Greenough, S. Roemer, D. Connor, A. L.
Gutt, B. Blair, G. Kanter and M. von Strandtmann, J. Antibiot.,
1977, 30, 371ꢀ375.
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DOI: 10.1039/C6RA02343F
Graphical Abstract
Synthesis of 4-trifluoromethanesulfonate substituted 3,6-
dihydropyrans and their application in various C-C coupling
reactions
Anil K. Saikia,*a Priya Ghosha and Ashutosh K. Kautarya a
One-pot, three component reaction of homopropargylic alcohols with aldehydes and triflic
acid afforded 3,6-dihydro-2H-pyran-4-yl trifluoromethanesulfonates via Prins cyclization
reaction in good yields. The dihydropyran thus formed is transformed into different 4-alkyl
and aryl substituted products using Suzuki, Heck, Stille and Sonogashira coupling reactions.